HIF-1α is necessary to support gluconeogenesis during liver regeneration

Toshihide Tajima, Nobuhito Goda, Natsuko Fujiki, Takako Hishiki, Yasumasa Nishiyama, Nanami Senoo-Matsuda, Motohide Shimazu, Tomoyoshi Soga, Yasunori Yoshimura, Randall S. Johnson, Makoto Suematsu

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    Abstract

    Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1α (HIF-1α) for hepatic glucose homeostasis during the reparative process, we inactivated the gene in hepatocytes in vivo. Following partial hepatectomy (PH), recovery of residual liver weight was initially retarded in the mutant mice by down-regulation of hepatocyte proliferation, but occurred comparably between the mutant and control mice at 72 h after PH. At this time point, the mutant mice showed lowered blood glucose levels with enhanced accumulation of glycogen in the liver. The mutant mice exhibited impairment of hepatic gluconeogenesis as assessed by alanine tolerance test. This appeared to result from reduced expression of PGK-1 and PEPCK since 3-PG, PEP and malate were accumulated to greater extents in the regenerated liver. In conclusion, these findings provide evidence for roles of HIF-1α in the regulation of gluconeogenesis under liver regeneration.

    Original languageEnglish
    Pages (from-to)789-794
    Number of pages6
    JournalBiochemical and Biophysical Research Communications
    Volume387
    Issue number4
    DOIs
    Publication statusPublished - 2009 Oct 2

    Fingerprint

    Hypoxia-Inducible Factor 1
    Liver Regeneration
    Gluconeogenesis
    Liver
    Hepatectomy
    Hepatocytes
    Glucose
    Recovery
    Liver Glycogen
    Glycogen
    Metabolism
    Alanine
    Blood Glucose
    Homeostasis
    Down-Regulation
    Genes
    Weights and Measures

    Keywords

    • Gluconeogenesis
    • Hypoxia inducible factor-1
    • Liver regeneration
    • Metabolome
    • Phosphoenolpyruvate carboxykinase
    • Phosphoglycerate kinase 1

    ASJC Scopus subject areas

    • Biochemistry
    • Biophysics
    • Cell Biology
    • Molecular Biology

    Cite this

    HIF-1α is necessary to support gluconeogenesis during liver regeneration. / Tajima, Toshihide; Goda, Nobuhito; Fujiki, Natsuko; Hishiki, Takako; Nishiyama, Yasumasa; Senoo-Matsuda, Nanami; Shimazu, Motohide; Soga, Tomoyoshi; Yoshimura, Yasunori; Johnson, Randall S.; Suematsu, Makoto.

    In: Biochemical and Biophysical Research Communications, Vol. 387, No. 4, 02.10.2009, p. 789-794.

    Research output: Contribution to journalArticle

    Tajima, T, Goda, N, Fujiki, N, Hishiki, T, Nishiyama, Y, Senoo-Matsuda, N, Shimazu, M, Soga, T, Yoshimura, Y, Johnson, RS & Suematsu, M 2009, 'HIF-1α is necessary to support gluconeogenesis during liver regeneration', Biochemical and Biophysical Research Communications, vol. 387, no. 4, pp. 789-794. https://doi.org/10.1016/j.bbrc.2009.07.115
    Tajima, Toshihide ; Goda, Nobuhito ; Fujiki, Natsuko ; Hishiki, Takako ; Nishiyama, Yasumasa ; Senoo-Matsuda, Nanami ; Shimazu, Motohide ; Soga, Tomoyoshi ; Yoshimura, Yasunori ; Johnson, Randall S. ; Suematsu, Makoto. / HIF-1α is necessary to support gluconeogenesis during liver regeneration. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 387, No. 4. pp. 789-794.
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